Streptococcal M protein promotes IL-10 production by cGAS-independent activation of the STING signaling pathway
(2018) In PLoS Pathogens 14(3).- Abstract
From an evolutionary point of view a pathogen might benefit from regulating the inflammatory response, both in order to facilitate establishment of colonization and to avoid life-threatening host manifestations, such as septic shock. In agreement with this notion Streptococcus pyogenes exploits type I IFN-signaling to limit detrimental inflammation in infected mice, but the host-pathogen interactions and mechanisms responsible for induction of the type I IFN response have remained unknown. Here we used a macrophage infection model and report that S. pyogenes induces anti-inflammatory IL-10 in an M protein-dependent manner, a function that was mapped to the B- and C-repeat regions of the M5 protein. Intriguingly, IL-10 was produced... (More)
From an evolutionary point of view a pathogen might benefit from regulating the inflammatory response, both in order to facilitate establishment of colonization and to avoid life-threatening host manifestations, such as septic shock. In agreement with this notion Streptococcus pyogenes exploits type I IFN-signaling to limit detrimental inflammation in infected mice, but the host-pathogen interactions and mechanisms responsible for induction of the type I IFN response have remained unknown. Here we used a macrophage infection model and report that S. pyogenes induces anti-inflammatory IL-10 in an M protein-dependent manner, a function that was mapped to the B- and C-repeat regions of the M5 protein. Intriguingly, IL-10 was produced downstream of type I IFN-signaling, and production of type I IFN occurred via M protein-dependent activation of the STING signaling pathway. Activation of STING was independent of the cytosolic double stranded DNA sensor cGAS, and infection did not induce detectable release into the cytosol of either mitochondrial, nuclear or bacterial DNA–indicating DNA-independent activation of the STING pathway in S. pyogenes infected macrophages. These findings provide mechanistic insight concerning how S. pyogenes induces the type I IFN response and identify a previously unrecognized macrophage-modulating role for the streptococcal M protein that may contribute to curb the inflammatory response to infection.
(Less)
- author
- Movert, Elin LU ; Lienard, Julia LU ; Valfridsson, Christine LU ; Nordström, Therése LU ; Johansson-Lindbom, Bengt LU and Carlsson, Fredric LU
- organization
- publishing date
- 2018-03-01
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS Pathogens
- volume
- 14
- issue
- 3
- article number
- e1006969
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- scopus:85044824499
- pmid:29579113
- ISSN
- 1553-7374
- DOI
- 10.1371/journal.ppat.1006969
- language
- English
- LU publication?
- yes
- id
- 593c9db9-97ad-4125-ab7e-46f2ef4149a0
- date added to LUP
- 2018-04-13 15:19:30
- date last changed
- 2024-07-08 12:38:32
@article{593c9db9-97ad-4125-ab7e-46f2ef4149a0, abstract = {{<p>From an evolutionary point of view a pathogen might benefit from regulating the inflammatory response, both in order to facilitate establishment of colonization and to avoid life-threatening host manifestations, such as septic shock. In agreement with this notion Streptococcus pyogenes exploits type I IFN-signaling to limit detrimental inflammation in infected mice, but the host-pathogen interactions and mechanisms responsible for induction of the type I IFN response have remained unknown. Here we used a macrophage infection model and report that S. pyogenes induces anti-inflammatory IL-10 in an M protein-dependent manner, a function that was mapped to the B- and C-repeat regions of the M5 protein. Intriguingly, IL-10 was produced downstream of type I IFN-signaling, and production of type I IFN occurred via M protein-dependent activation of the STING signaling pathway. Activation of STING was independent of the cytosolic double stranded DNA sensor cGAS, and infection did not induce detectable release into the cytosol of either mitochondrial, nuclear or bacterial DNA–indicating DNA-independent activation of the STING pathway in S. pyogenes infected macrophages. These findings provide mechanistic insight concerning how S. pyogenes induces the type I IFN response and identify a previously unrecognized macrophage-modulating role for the streptococcal M protein that may contribute to curb the inflammatory response to infection.</p>}}, author = {{Movert, Elin and Lienard, Julia and Valfridsson, Christine and Nordström, Therése and Johansson-Lindbom, Bengt and Carlsson, Fredric}}, issn = {{1553-7374}}, language = {{eng}}, month = {{03}}, number = {{3}}, publisher = {{Public Library of Science (PLoS)}}, series = {{PLoS Pathogens}}, title = {{Streptococcal M protein promotes IL-10 production by cGAS-independent activation of the STING signaling pathway}}, url = {{http://dx.doi.org/10.1371/journal.ppat.1006969}}, doi = {{10.1371/journal.ppat.1006969}}, volume = {{14}}, year = {{2018}}, }